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Wolff/Cope Approach to the AB Ring of the Sesterterpenoid Variecolin

Krout, Michael R. and Henry, Christopher E. and Jensen, Thomas and Wu, Kun-Liang (Phil) and Virgil, Scott C. and Stoltz, Brian M. (2018) Wolff/Cope Approach to the AB Ring of the Sesterterpenoid Variecolin. Journal of Organic Chemistry, 83 (13). pp. 6995-7009. ISSN 0022-3263. https://resolver.caltech.edu/CaltechAUTHORS:20180104-140230299

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Abstract

A stereoselective synthesis of the AB ring of the complex sesterterpenoid variecolin is presented. Our strategy features the development of a tandem Wolff/Cope rearrangement of α-diazo cyclobutyl ketones for the construction of fused, 8-membered carbocycles. Preliminary studies revealed a facile Wolff rearrangement but a difficult vinyl ketene cyclobutane Cope rearrangement. We have leveraged an efficient microwave-promoted tandem rearrangement to prepare the desired functionalized cyclooctadienones that we envision as potential key intermediates in the convergent synthesis of variecolin.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://dx.doi.org/10.1021/acs.joc.7b02972DOIArticle
http://pubs.acs.org/doi/10.1021/acs.joc.7b02972PublisherArticle
https://pubs.acs.org/doi/suppl/10.1021/acs.joc.7b02972PublisherSupporting Information
ORCID:
AuthorORCID
Krout, Michael R.0000-0002-0539-6986
Virgil, Scott C.0000-0001-8586-5641
Stoltz, Brian M.0000-0001-9837-1528
Additional Information:© 2018 American Chemical Society. Received: November 22, 2017; Published: January 4, 2018. Special Issue: Synthesis of Antibiotics and Related Molecules. The authors thank the NIH-NIGMS (R01GM080269), Eli Lilly (predoctoral fellowship to M.R.K.), the Danish Council for Independent Research/Natural Sciences (postdoctoral fellowship to T.J.), Amgen, AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim, Merck, and Caltech for generous financial support. Dr. Takeharu Toyoshima and Angela Guerrero are acknowledged for contributions to substrate preparation and reaction scouting. Drs. David VanderVelde and Scott Ross of the Caltech NMR facility are thanked for invaluable assistance with NMR experiments and helpful discussions. Lawrence Henling and Michael Day are gratefully acknowledged for X-ray crystallographic structural determination. Dr. Mona Shahgholi and Naseem Torian are acknowledged for assistance with high-resolution mass spectrometry. The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NIHR01GM080269
Eli LillyUNSPECIFIED
Danish Council for Independent Research-Natural SciencesUNSPECIFIED
AmgenUNSPECIFIED
AbbVieUNSPECIFIED
Bristol-Myers SquibbUNSPECIFIED
Boehringer-IngelheimUNSPECIFIED
MerckUNSPECIFIED
CaltechUNSPECIFIED
Issue or Number:13
Record Number:CaltechAUTHORS:20180104-140230299
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180104-140230299
Official Citation:Wolff/Cope Approach to the AB Ring of the Sesterterpenoid Variecolin. Michael R. Krout, Christopher E. Henry, Thomas Jensen, Kun-Liang Wu, Scott C. Virgil, and Brian M. Stoltz. The Journal of Organic Chemistry 2018 83 (13), 6995-7009 DOI: 10.1021/acs.joc.7b02972
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84082
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:04 Jan 2018 22:52
Last Modified:09 Mar 2020 13:19

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